Aggregation of poly(acrylic acid)-containing elastin-mimetic copolymers.

Bradford A Paik,Xinqiao Jia,Marco A Blanco,Kristi L Kiick,Christopher J Roberts

doi:10.1039/c4sm02525c

Abstract

Polymer-peptide conjugates were produced via the copper-catalyzed azide-alkyne cycloaddition of poly(tert-butyl acrylate) (PtBA) and elastin-like peptides. An azide-functionalized polymer was produced via atom transfer radical polymerization (ATRP) followed by conversion of bromine end groups to azide groups. Subsequent reaction of the polymer with a bis-alkyne-functionalized, elastin-like peptide proceeded with high efficiency, yielding di- and tri-block conjugates, which after deprotection, yielded poly(acrylic acid) (PAA)-based diblock and triblock copolymers. These conjugates were solubilized in dimethyl formamide, and addition of phosphate buffered saline (PBS) induced aggregation. The presence of polydisperse spherical aggregates was confirmed by dynamic light scattering and transmission electron microscopy. Additionally, a coarse-grained molecular model was designed to reasonably capture inter- and intramolecular interactions for the conjugates and its precursors. This model was used to assess the effect of the different interacting molecular forces on the conformational thermodynamic stability of the copolymers. Our results indicated that the PAA's ability to hydrogen-bond with both itself and the peptide is the main interaction for stabilizing the diblocks and triblocks and driving their self-assembly, while interactions between peptides are suggested to play only a minor role on the conformational and thermodynamic stability of the conjugates.

Highlights

IntroductionPeptide–polymer hybrid materials have the ability to combine advantageous chemical and physical properties, while overcoming the shortcomings of the individual component materials.[1,2] Many previously reported hybrid materials have demonstrated enhanced biological functionality, or control of assembly over multiple length scales.[1,3,4,5,6] This controlled assembly has resulted in versatile structures that have found application in numerous biological and non-biological applications.[7,8,9,10,11,12,13,14] Most commonly these structures are driven by hydrophobic interactions or triggering of speci c secondary structure in the peptide domains.[6,9,15,16] Of interest among these conjugates are materials with assembly that can be controlled via temperature,[17] pH, enzyme activity,[19,20] and ion/cofactors.[21]Triggered assembly by external stimuli allows for a greater level of control over the resulting structure of the hybrid conjugates
With the aim of producing conjugates that may capture the properties of select structural, multiblock proteins and show triggered assembly, we have previously reported the synthesis of a hybrid multiblock copolymer comprising poly(acrylic acid) (PAA) and a short elastin-like peptide (ELP).[22]
In an effort to produce computationally tractable systems aimed at understanding our previous results, we have synthesized diblock and triblock copolymers, VG2– PAA–VG2 and PAA–VG2 (Scheme 2) to enable study of the aggregation pathway

Summary

Introduction

Peptide–polymer hybrid materials have the ability to combine advantageous chemical and physical properties, while overcoming the shortcomings of the individual component materials.[1,2] Many previously reported hybrid materials have demonstrated enhanced biological functionality, or control of assembly over multiple length scales.[1,3,4,5,6] This controlled assembly has resulted in versatile structures that have found application in numerous biological and non-biological applications.[7,8,9,10,11,12,13,14] Most commonly these structures are driven by hydrophobic interactions or triggering of speci c secondary structure in the peptide domains.[6,9,15,16] Of interest among these conjugates are materials with assembly that can be controlled via temperature,[17] pH, enzyme activity,[19,20] and ion/cofactors.[21]Triggered assembly by external stimuli allows for a greater level of control over the resulting structure of the hybrid conjugates.

Methods

Results

Conclusion